P558: GERMAN AMLCG-SURVIVORSHIP STUDY – SOMATIC LONG-TERM CONSEQUENCE OF AML AND ITS THERAPY: FROM HEART TO KIDNEY.
Authors: A. S. Moret, E. Telzerow, C. Sauerland, M. Rothenberg-Thurley, F. H. A. Mumm, J. Braess, B. Wörmann, U. Krug, W. E. Berdel, W. Hiddemann, K. Spiekermann, P. Heußner, K. Kraywinkel, D. Görlich, K. H. Metzeler
Journal: HemaSphere (2022)

Background: As outcomes of patients with acute myeloid leukemia (AML) have improved, the fraction of patients surviving long-term are increasing. Information on somatic and psycho-social health consequences of AML and its treatment is sparse. Aims: Our aim was to perform a multi-dimensional analysis of health outcomes in AML long-term survivors (AML-LTS). This report focuses on somatic morbidity; overall and health-related quality of life are reported separately (Telzerow et al.). Methods: We conducted a cross-sectional study including AML survivors who had been enrolled in clinical trials or the patient registry of the AML-CG study group and were alive ≥5 years after initial diagnosis. Data concerning somatic health status were collected through patient questionnaires, assessment by the patients’ physicians, and medical and laboratory reports. An age- and sex-matched control cohort was derived from German population-based health surveys (Robert Koch Institute, DEGS1 survey; n=6013). Results: Data on somatic health status was available for 355 survivors, aged 28-93 years, who participated 5 to 19 years after their AML diagnosis. Thirty-eight percent of survivors were treated with chemotherapy with or without an autologous transplant, whereas 62% had undergone allogeneic transplantation (alloSCT). We compared the prevalence of somatic diseases between AML-LTS and the general German population (DEGS1 sample), focusing on cardiovascular diseases and risk factors due to their relevance for overall morbidity and mortality, and their known association with survivorship in other cancers. Using age- and sex-adjusted multivariate models (Figure A), we found that AML survivors had a 2-fold higher risk of type 1/2 diabetes (DM 1/2), and a 3.5-fold increased risk of congestive heart failure (CHF) compared to the general population. Prevalence of hypertension, coronary artery disease (CAD) and myocardial infarction were similar between the groups. To identify factors associated with development of CHF among AML-LTS, we constructed multivariate models incorporating patient- and treatment-related covariables. We found an increased risk of CHF for AML-LTS who have had AML relapse (OR, 3.16; 95% CI: 1.46 – 6.83; P=0.004) and, in trend, for patients with sAML or tAML (OR 2.19; 95%CI: 0.92 – 5.22, P=0.076). Disease- or treatment-related factors did not significantly associate with any of the other comorbidities we studied. Furthermore, AML-LTS had significantly impaired kidney function, as assessed by the glomerular filtration rate (eGFR) estimated using the CKD-EPI-formula. Figure B displays the median eGFR according to age groups for AML-LTS and DEGS1. For each age group AML-LTS had significantly lower eGFR in comparison to DEGS1. We did not find an association between kidney function and time since diagnosis (p=.5) and no differences between AML-LTS treated by chemotherapy or alloSCT (p=.5), survived a relapse (p=.9) or were diagnosed with de novo-AML vs. sAML/tAML (P=.6). Image:Summary/Conclusion: Compared to the German general population, AML-LTS had increased risks of CHF and diabetes, but not hypertension or CAD. We identified AML relapse as a risk factor for developing of CHF, suggesting that cumulative chemotherapy exposure might be causally involved. Notably, AML-LTS who had undergone alloSCT did not have increased risks of CHF, CAD, hypertension or diabetes, compared to survivors treated with chemotherapy only. In addition, AML-LTS had a higher prevalence of impaired renal function. We did not identify treatment- or disease-related factors that might cause the lower kidney function in AML-LTS.